Toxicity and response to ipilimumab and nivolumab in elderly patients with metastatic melanoma: A multicenter retrospective analysis.
Authors: Shivanshan Pathmanathan, Hari S Babu, Marcin Radoslaw Dzienis, Mary Azer, Melissa A. Eastgate
Journal: Journal of Clinical Oncology (2022)

e21540 Background: Dual immunotherapy (nivolumab and ipilimumab) is an effective therapy in the treatment of metastatic melanoma, however, its benefit in older patients is unclear. This study aims to investigate the impact of age on the efficacy and toxicity of dual immunotherapy. Methods: A multicentre retrospective study involving centres in Australia [Royal Brisbane and Women’s Hospital, Gold Coast University Hospital and Sunshine Coast University Hospital] was performed to compare the efficacy and toxicity of dual immunotherapy in metastatic melanoma in patients ≥65 years versus patients &lt; 65 years old treated between 2017 and 2021. Data collected included: baseline demographics, PFS, OS, Grade 3 or higher (Gr3+) adverse events as per CTCAEv5, discontinuation rate, duration and complications of steroids used to treat toxicity. Groups were compared using the Fisher exact test for categorical variables and Mann-Whitney test for continuous variables. Survival outcomes were compared using Kaplan Meier, Log rank test and multivariate Cox regression analysis. Results: A total of 139 patients were included with 52 patients ≥65 years and 87 patients &lt; 65 years. There were more males in patients ≥65years [78.9 v 59.8% p = 0.025], and a trend towards fewer BRAF mutations as expected [32.7 v 50.6% p = 0.053]. Other baseline characteristics were similar. Fewer patients received prior BRAF/MEK inhibitor therapy in patients ≥65 years [19.2 v 41.4% p = 0.009]. Median dose of ipilimumab received was 3 cycles in both groups. Median OS was similar in patients ≥65 years v &lt; 65 years [14.9 v 17.3mths p = 0.58]. Median progression free survival was also similar in patients ≥65 years v &lt; 65 years [7.1 v 6.9mths p = 0.79]. Age was not associated with a difference in overall survival on multivariate analysis. There was similar rates of Gr3+ adverse events in patients ≥65 years v &lt; 65 years [50 v 49% p = 1.0] and discontinuation rates secondary to toxicity [55.8 v 56% p = 1.0]. Arthritis lead to more discontinuation in the older patients [9.6% v 0% p = 0.006]. There was one death secondary to pancreatitis in a patient ≥65 years. Median duration of steroids used to treat adverse events was similar in patients ≥65 years v &lt; 65 years [12.2 v 11.7mths p = 0.46]. Complications of steroids requiring inpatient admission was numerically higher in the elderly population [41.3 v 20.4% p = 0.07]. The most common complication related to immunosuppression was infection. There were 2 deaths in patients ≥65 years secondary to infection while on higher dose steroids. Conclusions: Patients ≥65years received similar benefit from dual immunotherapy in comparison to their younger counterparts with similar toxicity. There was a trend towards greater number of complications secondary to steroids. Optimisation of steroid dose and duration in the older patients may reduce the above risk, while maintaining clinical benefit.